The present invention relates to a process for producing optically active compounds which are used as starting materials for optically active and physiologically active compounds, functional materials, etc., especially optically active hydroxy lactones.
Optically active compounds are useful as starting materials for physiologically active compounds such as pharmaceuticals, agricultural chemicals and so on, and functional materials, and as intermediates. However, since the compounds have optical isomers, one of the enantiomers is essentially used in practice. When the racemic compounds or compounds having a low optical purity are used, apparently no compounds having adequate physiological activity or functionality are obtained.
Optically active compounds obtained by the process of the present invention, namely hydroxy lactones, are very useful compounds. Nevertheless, an effective process of producing the compounds is unknown.
For instance, although a process for preparing derivatives from malic acid or malate obtained in nature is well-known, it is necessary to reduce either of two carboxyl groups or either of two esters. However, an effective process is unknown and the above process is not useful industrially. For obtaining an enantiomer, malic acid as the starting material which is not a natural type should be used. Since the compound is more expensive than that of a natural type, it is disadvantageous industrially for use as the starting material. (K. Mori et al., Tetrahedron, 35, 933(1979), H. Hayashi et al., J. Am. Chem. Soc., 95, 8749(1973), E. J. Corey et al., J. Am. Chem. Soc., 100, 1942(1978), S. J. Shiuey et al , J. Org. Chem., 53, 1040(1988)).
In addition, a process in which L-ascorbic acid is used as a starting material is known. However, the process is troublesome and disadvantageous (K. C. Luk et al., Synthesis, 3, 226(1988)).
Lately, a process for obtaining R-3-hydroxybutyrolactone is found by using baker's yeast. In the process, the effect of an asymmetrical reduction step in which the baker's yeast is used is not good. Namely, for example, one kg of baker's yeast, one kg of sucrose and 8 liters of water are used for treating only 35 g of substrate. The treatment is disadvantageous industrially. In the process, it is impossible to obtain an S-compound. For obtaining the S-compound, the other process should be studied. (D. Seebach, Synthesis, 1, 37(1986)).
Moreover, a method in which a prochiral ketone is asymmetrically reduced with optically active 4-methyl-1,4-dihydro pyridine to obtain S-pantolactone is known. Since the asymmetrical yield is low (about 72% ee), the method is rather impractical. (A. I. Meyers, Tetrahedron Letters, 29, 5617(1988)).
Further, a method for obtaining R- or S-pantolactone by an asymmetric alcoholysis in the presence of lipase has been reported. According to the method, it is possible to obtain both enantiomers. Although, it seems as if the method is excellent, the optical purity of the R-compound is 70% ee and that of S-compound is 36% ee. As a result, the method is impractical. (H. S. Bevinakatti, J. Org. Chem., 54, 2453(1989)).
As described above, the conventional methods have many problems. Firstly, starting materials obtained from natural products via many steps are expensive. Secondarily, since substrate concentration in a process of asymmetrical reduction is very low, the method is unsuitable for mass production. Thirdly, since only either enantiomer is obtainable, the other enantiomer should be obtained by a different method. Fourthly, it is impossible to obtain a compound having high purity.